Tang Yao Liang, Zhao Qiang, Qin Xinyu, Shen Leping, Cheng Leilei, Ge Junbo, Phillips M Ian
Department of Physiology and Biophysics, College of Medicine, University of South Florida, St. Petersburg, Florida, USA.
Ann Thorac Surg. 2005 Jul;80(1):229-36; discussion 236-7. doi: 10.1016/j.athoracsur.2005.02.072.
There are several reports that engrafted mesenchymal stem cells (MSCs) stimulate angiogenesis in the ischemic heart, but the mechanism remains controversial. We hypothesize that transplantation of MSCs enhances vascular regeneration through a paracrine action.
A transmural myocardial infarction was created by ligation of the left anterior descending coronary artery in rats. Those with an ejection fraction less than 0.70 1 week after myocardial infarction were included. Autologous MSCs (1 x 10(7); 0.2 mL) or culture medium (0.2 mL) was injected intramyocardially into the periinfarct zone (50 microL/injection at four sites; n = 20/group). At 2 weeks after transplantation, Western blot analysis was used to assay the paracrine factors and proapoptotic proteins. Echocardiography to assess heart function was performed on additional groups at 8 weeks after implantation.
The angiogenic factors basic fibroblast growth factor, vascular endothelial growth factor, and stem cell homing factor (stromal cell-derived factor -1alpha) increased in the MSC-treated hearts compared with medium-treated hearts. This was accompanied by a downregulation of proapoptotic protein Bax in ischemic myocardium. Similarly, capillary density increased about 40% in MSC-treated hearts compared with medium-treated hearts (p = 0.001). Left ventricular contractility, indicated by fractional shortening, improved in MSC-treated hearts at 2 months after implantation (MSCs: 48.6% +/- 19.9%; medium: 18.7% +/- 6.4%; p = 0.004).
Autologous MSC transplantation attenuates left ventricular remodeling and improves cardiac performance. The major mechanism appears to be paracrine action of the engrafted cells, increasing angiogenesis and cytoprotection.
有几份报告指出，植入的间充质干细胞（MSC）可刺激缺血心脏中的血管生成，但其机制仍存在争议。我们推测，MSC移植通过旁分泌作用增强血管再生。
通过结扎大鼠左前降支冠状动脉制造透壁性心肌梗死。纳入心肌梗死后1周射血分数小于0.70的大鼠。将自体MSC（1×10⁷；0.2 mL）或培养基（0.2 mL）心肌内注射到梗死周边区（四个部位各注射50 μL；每组n = 20）。移植后2周，采用蛋白质免疫印迹分析来检测旁分泌因子和促凋亡蛋白。在植入后8周，对其他组进行超声心动图检查以评估心脏功能。
与培养基处理的心脏相比，MSC处理的心脏中促血管生成因子碱性成纤维细胞生长因子、血管内皮生长因子和干细胞归巢因子（基质细胞衍生因子-1α）增加。这伴随着缺血心肌中促凋亡蛋白Bax的下调。同样，与培养基处理的心脏相比，MSC处理的心脏中毛细血管密度增加了约40%（p = 0.001）。植入后2个月，以缩短分数表示的左心室收缩力在MSC处理的心脏中有所改善（MSC组：48.6%±19.9%；培养基组：18.7%±6.4%；p = 0.004）。
自体MSC移植可减轻左心室重构并改善心脏功能。主要机制似乎是植入细胞的旁分泌作用，增加血管生成和细胞保护。
